One of the primary goals of geriatric medicine is the prevention of age-related disabilities. Physical exercise prevents disability primarily by improving skeletal muscle function. The interaction of genetic factors with behavior and medication use may explain the variability in individual response to the behavioral interventions. Recent evidence suggests that tissue angiotensin II production and the inflammatory response, and possibly the genes that regulate these processes, may play an important role in determining the physical function status. We propose to explore the associations of known and newly identified polymorphisms of the angiotensin converting enzyme (ACE) and cytokines genes with behavior and medication use in determining physical function in older persons. We will use data of the Health And Body Composition (HABC) cohort, and in two randomized trials of behavioral interventions and disability, the Fitness Arthritis and Seniors Trial (FAST) and the Arthritis, Diet and Activity Promotion Trial (ADAPT). These studies offer unique advantages, including the randomized behavioral interventions in the trials and the comprehensive phenotype definition of body composition, muscle performance, disability, disease and inflammation, available in the cohort. Our multidisciplinary team has experts in molecular biology, genetic epidemiology, bioinformatics, geriatrics, body composition, pharmacoepidemiology, biostatistics, and physical exercise and performance assessment. We will recall the FAST and ADAPT participants to collect genetic material and to assess long-term effects of the randomized interventions. We will use stored samples from HABC. We will assess associations of genetic polymorphisms with inflammation, body composition, muscle strength, physical performance and disability, in relation to physical exercise, diet and medication use. The results of the proposed study will provide data on effect size and variability of the association of individual genotypes with the physical function response to behavioral interventions and medication use. We will use the information on the gene polymorphisms, the associated phenotypes, the interventions, the optimal follow-up, and required sample size to design and implement a randomized trial to assess interactions of gene polymorphisms with behavioral and novel pharmacological interventions aimed to prevent the progression of disability by improving muscle strength.